Identifying direct target genes of Notch signaling in endothelial cells during endothelial-to-mesenchymal transition

Congenital heart defects due to anomalies in heart development occur in one percent of newborns. A critical event during heart development is the transformation of a subset of cells that line the inside of the heart, called endocardial cells, into mesenchymal cells. This process, termed endothelial-to-mesenchymal transition (EMT), generates cells to form heart valves and walls that divides the adult heart into chambers and regulates blood flow. If EMT does not progress properly, normal heart development is disrupted, resulting in the most common type of congenital heart defects. Notch proteins (signaling molecules that trigger genes to activate) play an important role in EMT as the activation of Notch signaling induces the EMT process in endothelial cells. Dr. Yangxin Fu’s research goal is to identify the direct target genes of Notch signaling that are critical to EMT. Using cell culture and molecular biology tools, including a cutting-edge, high throughput technique, Yangxin is analyzing thousands of candidate genes and searching for Notch target genes critical for EMT and heart development. This study will help to understand the molecular mechanism underlying the role of Notch signaling in EMT and in the long term it may find potential target molecules to prevent and treat the heart defects caused by disruption of Notch signaling.